Optoacoustic system for monitoring biodistribution of nanoparticles in vivo.

描述（由申请人提供）：我们提出了光声断层扫描的新应用，用于临床前研究中纳米颗粒生物分布的非侵入性和定量分析。目前，正在积极开发基于纳米技术的癌症和其他疾病的新疗法，这些疗法具有更高的特异性和更强的治疗潜力。迫切需要能够监测体内纳米颗粒的增殖和清除的低成本和高灵敏度仪器，以进行健康安全评估并确定疾病治疗的功效。目前的非侵入性纳米颗粒检测方法，如磁共振成像和放射成像（即计算机断层扫描及其变体）仍然昂贵，并且无法在临床实践中参与推进基于纳米技术的药物和治疗策略的许多企业。相反，对大量样品进行繁琐的事后分析仍然是进行纳米颗粒生物分布研究的常用方法。 光声层析成像是一种新型的成像技术，它利用组织的光学吸收特性和超声的高分辨率，对小动物的血管和内脏器官进行三维成像。由于各种各样的金和碳基纳米颗粒以及选择的可生物降解的纳米复合物已经表现出或可以被设计为在近红外光谱区域（所谓的生物透明窗口）中显示强光学共振，因此它们的少量可以用光声学在体内检测。在这项工作中，我们建议证明使用光声技术进行定量的金纳米棒和碳纳米管在小鼠体内的生物分布分析的可行性。我们的光声层析成像系统将检测吸收率的小体积变化，其对应于在特定波长处小于1%的器官吸收。我们建议在特定器官中建立吸收增加和纳米颗粒浓度之间的相关性，以允许在体内定量测量纳米颗粒。这将使我们能够定义我们的方法的灵敏度限制，并证明其在成本，多功能性，灵敏度和分辨率方面的优势，并评估其未来商业化的潜力。 PI是国际公认的光声成像技术及其商业化的领导者，将指导纳米技术和光声断层扫描方面的高素质专家团队成功完成项目。拟议的技术将导致商业仪器，将提供一个显着更便宜，更安全和更通用的替代目前的非侵入性成像方式，如CT和MRI。我们的成像系统将在纳米技术导向的生物工程企业和学术界有很高的需求，应用于新型纳米药物和纳米器件的药代动力学分析，生物分布研究和健康风险评估。 公共卫生相关性：需要能够在体内对纳米颗粒进行非侵入性和高灵敏度成像的高效且负担得起的成像技术来对纳米颗粒和基于纳米技术的新型药物进行健康风险评估和生物分布分析。在这里，我们证明了光声断层扫描能够检测少量的碳和金纳米粒子，并监测它们在体内的增殖。我们建议定义光声层析成像的灵敏度，并校准成像系统，以允许直接在小动物体内定量测量纳米颗粒浓度。提出了一种新颖，廉价和可靠的成像方式，以使企业和非营利研究人员有兴趣开发基于纳米技术的药物和疾病治疗，分析纳米颗粒带来的健康风险，并制定战略，以减少与纳米颗粒存在相关的不良反应。

DESCRIPTION (provided by applicant): We propose novel application of optoacoustic tomography for non-invasive and quantitative analysis of nanoparticle biodistribution in preclinical research. Novel nanotechnology-based treatments of cancer and other diseases with increased specificity and enhanced therapeutic potential are being actively developed at present. There is a pressing need for low-cost and high-sensitivity instrumentation capable of monitoring proliferation and clearance of nanoparticles in vivo to perform health safety assessments and determine efficacy of disease treatments. Current non-invasive methods of nanoparticle detection, such as magnetic resonance imaging and radiological imaging (i.e. computer tomography and its variants) remain expensive and are not accessible to many businesses involved in advancing nanotechnology-based drugs and therapeutic strategies in clinical practice. Instead, tedious post-mortem analysis of numerous samples remains a common method to perform nanoparticle biodistribution studies. Optoacoustic tomography is a novel imaging technology based on optical absorptivity of tissues and high resolution of ultrasound to produce three-dimensional images of vasculature and internal organs in small animals. Since a wide variety of gold and carbon-based nanoparticles, as well as select biodegradable nano- complexes already exhibit or can be engineered to display strong optical resonances in a near-infrared spectral region, a so-called biological transparency window, their small quantities can be detected in vivo with optoacoustics. In this work, we propose to demonstrate feasibility of using optoacoustic technology to perform quantitative biodistribution analysis of gold nanorods and carbon nanotubes in mice. Our optoacoustic tomography system will detect small volumetric changes in absoprtivity corresponding to less than 1 % of an organ absorbance at a specific wavelength. We propose to establish a correlation between absorption increase and a concentration of nanoparticles in a particular organ to allow quantitative measurements of nanoparticles in vivo. This will allow us to define sensitivity limits of our method and demonstrate its benefits in terms of cost, versatility, sensitivity and resolution and assess its potential for a future commercialization. The PI is an internationally recognized leader in optoacoustic imaging technology and its commercialization and will guide the team of highly qualified experts in nanotechnology and optoacoustic tomography towards successful completion of a project. The proposed technology will lead towards commercial instrumentation that will provide a significantly cheaper, safer and more versatile alternative to current non invasive imaging modalities, such as CT and MRI. Our imaging system will have a high demand in a nanotechnology-oriented bioengineering businesses and academic circles with applications in pharmacokinetics analysis, biodistribution studies and health risk assessments of novel nano-drugs and nano-devices. PUBLIC HEALTH RELEVANCE: Efficient and affordable imaging technologies capable of non-invasive and highly sensitive imaging of nanoparticles in vivo are needed to perform health risk assessment and biodistribution analysis of nanoparticles and novel nanotechnology-based drugs. Here we demonstrate that optoacoustic tomography is capable of detecting small quantities of carbon and gold nanoparticles and monitor their proliferation in vivo. We propose to define sensitivity of optoacoustic tomography and calibrate the imaging system to allow quantitave measurements of nanoparticle concentrations directly in small animals. Novel, inexpensive and reliable imaging modality is proposed to empower businesses and non-profit researchers interested in developing nanotechnology-based drugs and disease treatments, analyzing health risks presented by nanoparticles and developing strategies to reduce adverse effects associated with nanoparticle presence.